Mucolipin, TRPs and Human Disease

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DESCRIPTION (Provided By Applicant): Mucolipidosis Type IV (MLIV; MIM 252650) is a lysosomal storage disorder that is characterized by severe neurologic and ophthalmologic abnormalities. It is a progressive disease that usually presents during the first year of life with mental retardation, corneal opacities, and delayed motor milestones. Children with MLIV typically reach a maximum developmental level of 15 months in language and motor function, and are eventually totally blind. It is a rare autosomal recessive disease and the majority of patients diagnosed to date are of Ashkenazi Jewish descent. There is currently no treatment for this tragic disorder. Six months ago, three independent groups reported the cloning of the MLIV gene, MCOLN1. MCOLN1 is a new member of the Transient Receptor Potential (TRP) cation channel gene family. MCOLN1 encodes a protein called mucolipin that, like the other TRP genes, has six predicted transmembrane domains and a putative channel pore. The identification of mutations in MCOLN1 represents the first example of a neurological disease caused by a TRP-related channel. TRP genes were first described in Drosophila, and homology cloning has led to the identification of an entire mammalian TRP gene family. One member of this gene family, PKD2, is responsible for autosomal dominant polycystic kidney disease (ADPKD). PKD2 was cloned in 1996 and since that time, considerable progress has been made towards understanding the function of this gene. Together, MCOLN1 and PKD2 illustrate the importance of the TRP gene family in human health and disease. The goal of this workshop is to bring together scientists that work on MLIV and PKD with experts from the field of TRP channel characterization. The recent cloning of MCOLN1, coupled with the fact that it is a member of a rapidly growing and well-studied gene family, provides the justification for this workshop. In addition, a better understanding of the function of mucolipin provides hope to the MLIV families for an effective treatment aimed at abolishing the abnormal cellular storage in this devastating disease. We are certain that this workshop will integrate the most up-to-date information from the three disciplines, foster collaborations among researchers, and identify promising new avenues for research.